Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125(FAK), and paxillin

Neutrophil adhesion is fundamentally important during the onset of inflamma tory responses. The adhesion signaling pathways control neutrophil arrest a nd extravasation and influence neutrophil shape and function at sites of in flammation. In the present study the intracellular signaling pathways for t he adhesion of human neutrophils by pituitary growth hormone (GH) were exam ined, Pituitary GH triggered the tyrosine phosphorylation of Janus kinase 2 (Jak2) and STAT3 in neutrophils, In addition, pituitary GH treatment resul ted in the morphological changes and the tyrosine phosphorylation of focal adhesion kinase (p125(FAK)) and paxillin. Preincubation with genistein, a t yrosine kinase inhibitor, blocked the GH-stimulated adhesion and Jak2, STAT 3, p125(FAK), and paxillin phosphorylation. Confocal microscopy revealed th at pituitary GH stimulates the focal localization of p125(FAK), paxillin, p hosphotyrosine, and filamentous actin filament into the membrane rufflings and uropods of human neutrophils, Immunoprecipitation experiments revealed a physical association of Jak2 with p125(FAK) via STAT3 in vivo. Also an in vitro kinase assay showed an augmentation of p125(FAK) autophosphorylation as a result of pituitary GH treatment. These results suggest that pituitar y GH modulates neutrophil adhesion through tyrosine phosphorylation of Jak2 , p125(FAK), and paxillin and actin polymerization.